vx-770 and Gastroesophageal-Reflux

Several new therapeutic modalities have recently become available to be used in patients with cystic fibrosis such as potentiators, modulators, and probiotics. Although the effects on pulmonary function have been well documented, gastrointestinal outcomes have been addressed only rarely.. Both the potentiator (ivacaftor) and the potentiator/modulator combination (ivacaftor/lumacaftor) that are currently on the market have a positive effect on BMI. Young patients (2-5 years of age) with a gating mutation may show improvement of exocrine pancreatic function on ivacaftor. In this specific patient population this agent also seems to improve intestinal pH and reflux. The effect of these medications on other gastrointestinal outcomes, such as intestinal inflammation and cystic fibrosis liver disease, has not been described so far. Furthermore, the results of several trials suggest that probiotics might reduce intestinal inflammation. Finally, organoids might be used to predict in vitro the clinical effect of potentiators and modulators.. The effect of new interventions on the gastrointestinal outcomes studied so far is favourable. Future studies should address the effect on other gastrointestinal parameters.

Topics: Aminophenols; Aminopyridines; Benzodioxoles; Body Mass Index; Chloride Channel Agonists; Cystic Fibrosis; Digestive System; Drug Combinations; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Intestinal Diseases; Liver Diseases; Probiotics; Quinolones; Treatment Outcome; Weight Gain

Topics: Adolescent; Aminophenols; Benzodioxoles; Chloride Channel Agonists; Cystic Fibrosis Transmembrane Conductance Regulator; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Mutation

Extra-oesophageal reflux (EOR) may lead to microaspiration in patients with cystic fibrosis (CF), a probable cause of deteriorating lung function. Successful clinical trials of ivacaftor highlight opportunities to understand EOR in a real world study.. Data from 12 patients with CF and the G551D mutation prescribed ivacaftor (150mg bd) was collected at baseline, 6, 26 and 52weeks. The changes in symptoms of EOR were assessed by questionnaire (reflux symptom index (RSI) and Hull airway reflux questionnaire (HARQ)).. Six patients presented EOR at baseline (RSI >13; median 13; range 2-29) and 5 presented airway reflux (HARQ >13; median 12; range 3 to 33). Treatment with ivacaftor was associated with a significant reduction of EOR symptoms (P<0∙04 versus baseline) denoted by the reflux symptom index and Hull airway reflux questionnaire.. Ivacaftor treatment was beneficial for patients with symptoms of EOR, thought to be a precursor to microaspiration.

Topics: Adult; Aminophenols; Chloride Channel Agonists; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Drug Monitoring; Female; Gastroesophageal Reflux; Humans; Lung; Male; Mutation; Quinolones; Respiratory Aspiration; Respiratory Function Tests; Treatment Outcome; United Kingdom